In a single-institution phase II trial reported in the Journal of Clinical Oncology, Jain et al found that chemotherapy-free treatment with the combination of ibrutinib and rituximab produced high overall and complete response rates in patients with previously untreated mantle cell lymphoma aged ≥ 65 years. Atrial fibrillation was observed in a third of patients.
The trial enrolled 50 patients at The University of Texas MD Anderson Cancer Center between October 2015 and November 2019. Patients with a Ki67 level of > 50% and blastoid morphology were excluded. Ibrutinib was given at 560 mg once daily in 28-day cycles. Rituximab was given at 375 mg/m2 once weekly for 4 weeks in cycle 1, on day 1 of every cycle starting in cycles 3 to 8, and on day 1 every 2 months for up to 2 years after cycle 8; after 2 years, ibrutinib was given in continuous cycles until disease progression or unacceptable toxicity. None of the patients received stem cell transplantation.
Median follow-up was 45 months (interquartile range = 24–56 months). In intent-to-treat analysis, objective response was observed in 46 (92%) of 50 patients, with complete response in 34 (68%). Among 48 patients evaluable for response, objective response was observed in 96%, with complete response in 71%. In analysis according to Ki67 percentage, objective response was observed in 37 (97%; complete response in 74%) of 38 patients with a Ki67 level of < 30% and in 9 (75%; complete response in 50%) of 12 with a Ki67 level of ≥ 30% to 50% (P < .001).
Among 16 responders with baseline samples assessed by bulk RNA sequencing, differential overexpression of CCND1, BIRC3, BANK1, SETBP1, AXIN2, and IL2RA was observed among 7 patients with partial response vs 9 with complete response.
Median progression-free survival and median overall survival were not reached; 3-year rates were 87% (95% confidence interval [CI] = 73%–94%) and 94% (95% CI = 82%–98%), respectively. A trend toward improved progression-free survival among patients with lower Ki67 was observed (hazard ratio = 2.62) but was not statistically significant (P = .190). No difference in overall survival was observed according to Ki67 percentage (P = .356).
The most common grade 3 or 4 adverse events were atrial fibrillation (22%), fatigue (18%), diarrhea (14%), and myalgia (14%). Grade 3 or 4 hematologic toxicities consisted of neutropenia in 8% of patients, and anemia and thrombocytopenia in 4% each. Four patients developed grade 3 or 4 bleeding while on ibrutinib. Overall, 17 patients (34%) developed atrial fibrillation, which resulted in discontinuation of ibrutinib in 10 participants; of the 17 patients, 9 had no history of atrial fibrillation. No treatment-related deaths were observed.
The investigators concluded, “Ibrutinib/rituximab combination is effective in older patients with mantle cell lymphoma. Baseline evaluation for cardiovascular risks is highly recommended. [A] randomized trial is needed for definitive conclusions.”
Michael L. Wang, MD, of the Department of Lymphoma & Myeloma, The University of Texas MD Anderson Cancer Center, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by Pharmacyclics LLC and Janssen. For full disclosures of the study authors, visit ascopubs.org.The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.